Phenylketonuria is an inborn error of metabolism characterized by high levels of the amino acid phenylalanine [Phe] in the blood of newborns. PKU is diagnosed by means of the Guthrie Test., devised by Dr Robert Guthrie (1916 - 1995) after the birth of his own child with PKU. A small drop of blood is taken from the heel of a newborn (left) and applied to a card [right]. In the original form of the test, a punch-out of the dried disc was incubated on a petri dish plated with bacteria (Bacillus subtilis) in the presence of a growth inhibitor, B-2-thienyl-alanine. High levels of Phe in the blood sample overcome the inhibition, and allow the bacteria to grow. If an elevated level of Phe is detected, the child is placed on a phenylalanine-restricted diet for the first several years (< 10 years). This can completely offset the expected neurological effects (below). The Guthrie test was the first widely-used perinatal biochemical test, and since its introduction in the early 1960s has been used in >90% of North American hospitals.

    The original test has been supplanted by direct mass-spectroscopy measurement of Phe concentration. Children in families at risk for PKU may also be screened by prenatal PCR-based DNA tests for the PKU-related alleles themselves.

    Recent evidence suggests that high levels of [Phe] may impair mental performance later in life, and that a Phe-restricted diet should be maintained throughout life. As well, if the diet is discontinued during pregnancy, PKU mothers who have been successfully treated early in life may introduce high levels of Phe into the fetal circulation; this may cause maternal PKU in a developing fetus that does not have the PKU genotype.